Comparison of biological properties of 111In-labeled dimeric cyclic RGD peptides

Zheng, Yu; Ji, Shundong; Tomaselli, Elena; Yang, Yong; Liu, Shuang

doi:10.1016/j.nucmedbio.2014.10.005

Cited by 14 publications

(15 citation statements)

References 48 publications

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“…19,21,30 The in vitro assays and biodistribution data clearly showed that the radiolabeled dimeric and tetrameric cyclic RGD peptides have higher α v β 3 binding affinity and better tumor uptake than their corresponding monomeric analogs. 19,21,30,34–50 …”

Section: Maximizing Binding Affinity Via Multimerizationmentioning

confidence: 99%

“…Different linkers (Figure 6) have been proposed to increase the distance between two RGD motifs and improve pharmacokinetics of radiotracers. 38–42,47–50 The results from in vitro and in vivo assays showed that the linkers (G 3 vs. D 3 and PEG 4 or PEG 4 vs. SAA, 1,2,3-triazole and PEG 2 moieties) have little impact on the α v β 3 binding affinity of HYNIC-conjugated dimeric cyclic RGD peptides (Table 1) as long as they are long enough for bivalency. However, the overall molecular charges may have significant impact on the radiotracer uptake in both tumors and normal organs.…”

Section: Maximizing Binding Affinity Via Multimerizationmentioning

confidence: 99%

“…To keep the consistency and reproducibility, we have been using U87MG glioma cells (high α v β 3 and α v β 5 expression) as the “host cells” and 125 I-echistatin as the radioligand. 34–50 Since the whole-cell displacement assay is operator-dependent, caution should be taken when comparing their IC 50 values with those reported in the literature. Whenever possible, a “control compound”, such as c(RGDfK) or c(RGDyK) should be used in each experiment.…”

Section: Important Biological Assaysmentioning

confidence: 99%

“…Our studies show that radiolabeled tetrameric cyclic RGD peptides have higher uptake than their dimeric analogs in both tumors and α v β 3 -positive organs. 33,50 High tumor uptake is important for the sensitivity, but their potential as tumor imaging agents will rely upon the contrast between tumor and normal tissues. There is always a subtle balance between the tumor uptake and T/B ratios.…”

Section: New Opportunities and Challengesmentioning

confidence: 99%

“…11–50 A number of review articles have appeared to cover their nuclear medicine applications. 51–65 Instead of being an exhaustive review of current literature on radiolabeled cyclic RGD peptides, this article will use the dimeric and tetrameric cyclic RGD peptides developed in our laboratories as examples to illustrate the basic principles for development of α v β 3 -targeted radiotracers.…”

Section: Introductionmentioning

confidence: 99%

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Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Liu

2015

Bioconjugate Chem.

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Angiogenesis is a requirement for tumor growth and metastasis. The angiogenic process depends on vascular endothelial cell migration and invasion, and is regulated by various cell adhesion receptors. Integrins are such a family of receptors that facilitate the cellular adhesion to and migration on extracellular matrix proteins in the intercellular spaces and basement membranes. Among 24 members of the integrin family, αvβ3 is studied most extensively for its role in tumor angiogenesis and metastasis. The αvβ3 is expressed at relatively low levels on epithelial cells and mature endothelial cells, but it is highly expressed on the activated endothelial cells of tumor neovasculature and some tumor cells. This restricted expression makes αvβ3 an excellent target to develop antiangiogenic drugs and diagnostic molecular imaging probes. Since αvβ3 is a receptor for extracellular matrix proteins with one or more RGD tripeptide sequence, many radiolabeled cyclic RGD peptides have been evaluated as “αvβ3–targeted” radiotracers for tumor imaging over the last decade. This article will use the dimeric and tetrameric cyclic RGD peptides developed in our laboratories as examples to illustrate basic principles for development of αvβ3–targeted radiotracers. It will focus on different approaches to maximize the radiotracer tumor uptake and tumor/background ratios. This article will also discuss some important assays for pre-clinical evaluations of integrin–targeted radiotracers. In general, multimerization of cyclic RGD peptides increases their integrin binding affinity and the tumor uptake and retention times of their radiotracers. Regardless of their multiplicity, the capability of cyclic RGD peptides to bind other integrins (namely αvβ5, α5β1, α6β4, α4β1 and αvβ6) is expected to enhance the radiotracer tumor uptake due to the increased integrin population. The result from preclinical and clinical studies clearly show that radiolabeled cyclic RGD peptides (such as 99mTc-3P-RGD2, 18F-Alfatide-I and 18F-Alfatide-II) are useful as the molecular imaging probes for early cancer detection and noninvasive monitoring of the tumor response to antiangiogenic therapy.

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Section: Maximizing Binding Affinity Via Multimerizationmentioning

confidence: 99%

Section: Maximizing Binding Affinity Via Multimerizationmentioning

confidence: 99%

Section: Important Biological Assaysmentioning

confidence: 99%

Section: New Opportunities and Challengesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Liu

2015

Bioconjugate Chem.

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Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging

2016

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The integrin family comprises 24 transmembrane receptors, each a heterodimeric combination of one of 18α and one of 8β subunits. Their main function is to integrate the cell adhesion and interaction with the extracellular microenvironment with the intracellular signaling and cytoskeletal rearrangement through transmitting signals across the cell membrane upon ligand binding. Integrin αvβ3 is a receptor for the extracellular matrix proteins containing arginine–glycine–aspartic (RGD) tripeptide sequence. The αvβ3 is generally expressed in low levels on the epithelial cells and mature endothelial cells, but it is highly expressed in many solid tumors. The αvβ3 levels correlate well with the potential for tumor metastasis and aggressiveness, which make it an important biological target for development of antiangiogenic drugs, and molecular imaging probes for early tumor diagnosis. Over the last decade, many radiolabeled cyclic RGD peptides have been evaluated as radiotracers for imaging tumors by SPECT or PET. Even though they are called “αvβ3-targeted” radiotracers, the radiolabeled cyclic RGD peptides are also able to bind αvβ5, α5β1, α6β4, α4β1, and αvβ6 integrins, which may help enhance their tumor uptake due to the “increased receptor population.” This article will use the multimeric cyclic RGD peptides as examples to illustrate basic principles for development of integrin-targeted radiotracers and focus on different approaches to maximize their tumor uptake and T/B ratios. It will also discuss important assays for pre-clinical evaluations of the integrin-targeted radiotracers, and their potential applications as molecular imaging tools for noninvasive monitoring of tumor metastasis and early detection of the tumor response to antiangiogenic therapy.

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68Ga-labeled dimeric and trimeric cyclic RGD peptides as potential PET radiotracers for imaging gliomas

Zhao

Ji²,

et al. 2019

Applied Radiation and Isotopes

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Comparison of biological properties of 111In-labeled dimeric cyclic RGD peptides

Cited by 14 publications

References 48 publications

Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging

68Ga-labeled dimeric and trimeric cyclic RGD peptides as potential PET radiotracers for imaging gliomas

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